title: Safety and immunogenicity of a candidate therapeutic vaccine, p24 virus-like particle, combined with zidovudine, in asymptomatic subjects. Community HIV Research Network Investigators.
abstract: OBJECTIVE
  To evaluate the impact of therapeutic immunization with p24 virus-like particle (VLP) and zidovudine (ZDV) on p24 antibody titre (primary endpoint), CD4+ cell counts, cellular responses to the immunogen and recall antigens, and viral load (secondary endpoints) in subjects with asymptomatic HIV infection and CD4+ counts greater than 400 x 10(6) cells/l.
  
  
  METHODS
  A double dummy, double-blind randomized placebo-controlled Phase II trial of the therapeutic vaccine p24-VLP, with or without ZDV.
  
  
  METHODS
  ZDV-naive subjects were randomized to one of three groups for 6 months: group A, ZDV 200 mg three times daily plus intramuscular administration of alum adjuvant monthly; group B, ZDV 200 mg three times daily plus p24-VLP (500 microg) in intramuscular alum monthly; group C, placebo capsules plus p24-VLP (500 microg) in intramuscular alum monthly. Subjects were followed for a further 6 months.
  
  
  RESULTS
  Sixty-one patients received vaccinations. The mean CD4+ cell counts pretherapy for groups A, B, and C were 605 +/- 25, 668 +/- 43, and 583 +/- 30 x 10(6) cells/l, respectively. Treatment was well tolerated. At both 24 and 52 weeks there were no significant differences between the treatment groups in terms of antibody responses to p24, CD4+ or CD8+ cell counts, viral load, T-cell responses to p24, p17, recall antigen or mitogen, or markers of immune activation, despite induction of antibody and proliferative responses to the carrier protein of the vaccine.
  
  
  CONCLUSIONS
  Vaccination with p24-VLP was well tolerated. p24-VLP either alone or in combination with ZDV did not significantly alter either antibody or proliferative responses to p24, or CD4+ cell number, immune activation or viral load over 12 months.
authors.affiliation: Centre for Immunology, St Vincent's Hospital, University of New South Wales, Darlinghurst, Australia.
authors.forename: A D
authors.initials: AD
authors.lastname: Kelleher
authors.forename: M
authors.initials: M
authors.lastname: Roggensack
authors.forename: A B
authors.initials: AB
authors.lastname: Jaramillo
authors.forename: D E
authors.initials: DE
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Walker
authors.forename: I
authors.initials: I
authors.lastname: Gow
authors.forename: M
authors.initials: M
authors.lastname: McMurchie
authors.forename: J
authors.initials: J
authors.lastname: Harris
authors.forename: G
authors.initials: G
authors.lastname: Patou
authors.forename: D A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D016655:HIV Core Protein p24 / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D006801:Humans; D006968:Hypersensitivity, Delayed; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014611:Vaccination; D019562:Viral Load; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D015483:HIV Antibodies; D016655:HIV Core Protein p24; C065031:p24-VLP vaccine; D015215:Zidovudine